Developmental origin of oligodendrocytes determines their function in the adult brain

Author:

Foerster Sarah,Floriddia Elisa M.ORCID,van Bruggen DavidORCID,Kukanja PetraORCID,Hervé BastienORCID,Cheng Shangli,Kim EosuORCID,Phillips Benjamin U.,Heath Christopher J.,Tripathi Richa B.,Call CodyORCID,Bartels Theresa,Ridley Katherine,Neumann Björn,López-Cruz Laura,Crawford Abbe H.,Lynch Cian J.,Serrano ManuelORCID,Saksida Lisa,Rowitch David H.ORCID,Möbius WiebkeORCID,Nave Klaus-ArminORCID,Rasband Matthew N.ORCID,Bergles Dwight E.ORCID,Kessaris NicolettaORCID,Richardson William D.ORCID,Bussey Timothy J.ORCID,Zhao ChaoORCID,Castelo-Branco GonçaloORCID,Franklin Robin J. M.ORCID

Abstract

AbstractIn the mouse embryonic forebrain, developmentally distinct oligodendrocyte progenitor cell populations and their progeny, oligodendrocytes, emerge from three distinct regions in a spatiotemporal gradient from ventral to dorsal. However, the functional importance of this oligodendrocyte developmental heterogeneity is unknown. Using a genetic strategy to ablate dorsally derived oligodendrocyte lineage cells (OLCs), we show here that the areas in which dorsally derived OLCs normally reside in the adult central nervous system become populated and myelinated by OLCs of ventral origin. These ectopic oligodendrocytes (eOLs) have a distinctive gene expression profile as well as subtle myelination abnormalities. The failure of eOLs to fully assume the role of the original dorsally derived cells results in locomotor and cognitive deficits in the adult animal. This study reveals the importance of developmental heterogeneity within the oligodendrocyte lineage and its importance for homeostatic brain function.

Publisher

Springer Science and Business Media LLC

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